This project focuses on the effects of cocaine abuse on brain blood flow and the manner in which certain treatments might protect against those effects. Four groups of cocaine abusers (N=48) stratified for age, gender, ethnicity, and cocaine-use history, are enrolled in a randomized, double-blind, placebo-controlled, human-laboratory study assessing the effects of cocaine dosage on restricting blood flow in certain brain regions (e.g. dopamine-innervated areas), and the ability of isradipine, an L-type calcium-channel blocker, to improve blood flow. A novel quantitative approach to Single Photon Emission Tomography (SPECT) is coupled with structural Magnetic Resonance Imaging (MRI) to examine cerebral blood flow. In addition, we will also analyze our SPECT data using state-of-the-art voxel-based analyses co-registered to Talairach space using an internal landmark registration system (i.e., Statistical Parametric Mapping); thereby providing further validation of the novel SPECT technique and permitting direct comparison of our data with the published literature and other ongoing studies. Subjective effects (e.g. abuse-potential, craving, euphoria, and stimulant side-effects) are also assessed before and after cocaine and isradipine treatments. This study tests mechanistic hypotheses that will lead to new information about: a) the relationships between the neural, behavioral, and rewarding effects of cocaine and its treatment; b) a unique strategy for assessing the effects of cocaine-abuse treatments, and c) a potential new strategy for cocaine-abuse treatment based on preventing cocaine-induced decreases in blood flow to specific brain regions.